We propose to develop several methods for the assay of diethylstilbestrol (DES), diethylstilbestrol diphosphate (stilphostrol), the parenteral pro-drug form of DES, and their metabolites in plasma and tissues using gas chromatographic and mass spectrometric (GC/MS) techniques. Our GC/MS method involves the controlled degradation of the phosphate forms of DES into differentially derivatized DES molecules which will be individually quantified by selected ion recording. It is our plan to study the physiological disposition of those two agents, i.e., their distribution, metabolism, excretion and pharmacokinetics, in dogs and in patients with prostatic carcinoma. We will determine the biological half lives, volumes of distribution and extent of protein binding of each chemical species. Such data from humans has not previously been published. Of particular emphasis in our study is the generation of data which can be fit by an analog computer model of the disposition of each agent. With this model we can simulate potentially improved dosage regimens of DES and stilphostrol. We propose to examine the extent to which the improved therapeutic benefit of stilphostrol is due to preferential concentration of DES by prostatic tissues.